The relationship between the insulin-like growth factor-1 system and the oestrogen metabolising enzymes in breast cancer tissue and its adjacent non-cancerous tissue

Chong, Yeeting E.; Colston, Kay W.; Jiang, Wen Guo; Sharma, Anup; Mokbel, K.

doi:10.1007/s10549-006-9215-y

Cited by 21 publications

(17 citation statements)

References 85 publications

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“…this result is consistent with previously described data obtained in mice, where the overexpression of IGF1R facilitated tumor development (36,37). Moreover, increased expression of IGF1R has been linked to several cancer types in humans (38,39). It has been proposed that the up-regulation of iGF1r in cancer cells may be due to loss of transcriptional control by major tumor-suppressor genes (40).…”

Section: Discussionsupporting

confidence: 92%

IGF1 mRNA isoform expression in the cervix of HPV-positive women with pre-cancerous and cancer lesions

Koczorowska

Kwaśniewska

Goździcka-Józefiak

2010

Experimental and Therapeutic Medicine

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Abstract. human papillomavirus (hpV) plays a crucial role in cervical cancer etiology. however, not all hpV-infected women develop cancer, indicating that additional cellular factors facilitate carcinogenesis. the aim of this study was to analyze the expression profile of insulin-like growth factor 1 (iGF1) isoforms in the context of FOx2, Sp1 and iGF1 receptor (iGF1r) expression during hpV-dependent cervical carcinogenesis. One hundred and nine epithelial tissue samples from women with pre-cancerous and cancer lesions of the cervix were analyzed. HPV DNA was identified by pcr, and real-time pcr was used to quantify the expression levels of the analyzed genes. all IGF1 mrna splicing isoforms were up-regulated in pre-cancerous cells, and a shift in the balance towards mitogenic iGF1Eb was observed in the cancer samples. IGF1 expression was controlled mainly by the p1 promoter, and an increase in p2 usage was observed in the cancer. correlations between IGF1 mrna splicing isoforms and the FOx2 splicing factor, as well as p1/p2 activity and Sp1 transcription factor expression levels were detected. no correlation was observed between the expression of iGF1 and its receptor iGF1r. Our results suggest that iGF1, in particular its splicing profile, may be an additional prognostic factor in cervical carcinogenesis.

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Section: Discussionsupporting

confidence: 92%

IGF1 mRNA isoform expression in the cervix of HPV-positive women with pre-cancerous and cancer lesions

Koczorowska

Kwaśniewska

Goździcka-Józefiak

2010

Experimental and Therapeutic Medicine

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“…This is consistent with TFF1 and PGR being known to be regulated by estrogen and the presence of higher levels of ESR1 in the malignant tissue than in adjacent normal tissue. We did not see any significant differences in the expression of CYP19, HSD17B1, and HSD17B2 between normal breast and malignant tissues, in agreement with the results of other studies of more heterogeneous patient groups (42,44,45). The consistent finding that CYP19 does not show increased expression in tumor compared with normal tissue may be a reflection of its very low activity within the breast, which makes accurate measurement of CYP19 mRNA, protein, or enzyme activity difficult.…”

Section: Discussionsupporting

confidence: 90%

Intratumoral Estrogen Disposition in Breast Cancer

Haynes

Straume

Geisler

et al. 2010

Clinical Cancer Research

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Purpose: The concentration of estradiol (E 2 ) in breast tumors is significantly higher than that in plasma, particularly in postmenopausal women. The contribution of local E 2 synthesis versus uptake of E 2 from the circulation is controversial. Our aim was to identify possible determinants of intratumoral E 2 levels in breast cancer patients.Experimental Design: The expression of genes involved in estrogen synthesis, metabolism, and signaling was measured in 34 matched samples of breast tumor and normal breast tissue, and their correlation with estrogen concentrations assessed.Results: ESR1 (9.1-fold; P < 0.001) and HSD17B7 (3.5-fold; P < 0.001) were upregulated in ER + tumors compared with normal tissues, whereas STS (0.34-fold; P < 0.001) and HSD17B5 (0.23-fold; P < 0.001) were downregulated. Intratumoral E 2 levels showed a strong positive correlation with ESR1 expression in all patients (Spearman r = 0.55, P < 0.001) and among the subgroups of postmenopausal (r = 0.76, P < 0.001; n = 23) and postmenopausal ER + patients (r = 0.59, P = 0.013; n = 17). HSD17B7 expression showed a significant positive correlation (r = 0.59, P < 0.001) whereas HSD17B2 (r = −0.46, P = 0.0057) and HSD17B12 (r = −0.45, P = 0.0076) showed significant negative correlations with intratumoral E 2 in all patients. Intratumoral E 2 revealed no correlation to CYP19, STS, and HSD17B1 expression. Multivariate models comprising ESR1 and plasma E 2 predicted between 50% and 70% of intratumoral E 2 variability.

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“…IGF1R expression was detected in a higher proportion of luminal A tumors, followed by luminal B and HER2-positive tumors, with the lowest rate in basal/triple-negative, in line with previous investigators who reported co-expression of IGF1R and ER signaling systems. 19,24,25,32 The presence of IGF1R in tumors with higher content of ER/PR support the development of a subset of breast carcinoma subtypes along these two distinct pathways, mainly luminal A and B. It is plausible that together with microenvironment interactions and/or additional gene alterations, it might contribute to tumor heterogeneity.…”

Section: Discussionmentioning

confidence: 99%

“…[9][10][11][12] Recent epidemiological and clinico-pathological data have supported the role of the insulin-like growth factor-1 (IGF1R) signaling system on tumor development and progression. [13][14][15][16][17] In breast carcinoma, high levels of IGF1R have been detected in 30-82%, 18,19 but its prognostic value is controversial. [20][21][22][23][24][25][26][27] Emerging experimental and clinical data suggest that the IGF1R and ER/PR pathways are interactive.…”

mentioning

confidence: 99%

Increased insulin-like growth factor-1 receptor mRNA expression predicts poor survival in immunophenotypes of early breast carcinoma

et al. 2011

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The biology of breast carcinoma shows a great variation, reflected by the recent classification of phenotypes based on DNA microarrays or immunohistochemistry. The aim of this study was to determine the prevalence of insulin-like growth factor-1 receptor (IGF1R) in breast carcinoma subtypes and the impact on the outcome. We studied 197 consecutive breast carcinoma patients in stage I-II treated conservatively. Phenotypes were assessed on the basis of the expressions of ER/PR, HER2, Ki67, p53, Bcl2, CK5/6 and EGFR. Moreover, IGF1R expression (a-subunit and b-phosphorylated/active form) was evaluated by immunohistochemistry, IGF1R mRNA levels by quantitative RT-PCR and IGF1R mutations by direct DNA sequencing. Overall, 40% (78/197) of tumors were luminal A, 24% (48/197) luminal B, 19% (37/197) HER2-positive and 17% (34/197) basal/triplenegative. Luminal A tumors were predominantly of low grade, without necrosis, presenting in older patients as a r2-cm unilateral mass (all Pr0.046). a-IGF1R overexpression was observed more frequently in luminal A (49%) cases, followed by luminal B (20%), HER2-positive area under the curve (22%) and basal/triple-negative cases (9%) (P ¼ 0.01) with similar results for mRNA levels (53, 24, 13 and 10%, respectively) (P ¼ 0.038), but without differences for mutations (P ¼ NS). High IGF1R mRNA correlated with poor patient survival among subtypes (P ¼ 0.004) (Kaplan-Meier; log-rank test). For overall survival, only histological grade and IGF1R mRNA emerged as significant predictors (Pr0.034; Cox regression). Increased IGF1R mRNA implies poorer patient prognosis among the different subtypes, and that may be associated with the lack of responsiveness to tamoxifen in cases with a positive hormone receptor status. Our results highlight the biological and clinical relevance of IGF1R in early breast carcinoma subtypes, and provide knowledge to assist in treatment decision.

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The relationship between the insulin-like growth factor-1 system and the oestrogen metabolising enzymes in breast cancer tissue and its adjacent non-cancerous tissue

Cited by 21 publications

References 85 publications

IGF1 mRNA isoform expression in the cervix of HPV-positive women with pre-cancerous and cancer lesions

IGF1 mRNA isoform expression in the cervix of HPV-positive women with pre-cancerous and cancer lesions

Intratumoral Estrogen Disposition in Breast Cancer

Increased insulin-like growth factor-1 receptor mRNA expression predicts poor survival in immunophenotypes of early breast carcinoma

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